: Introduction: This is a proposal to continue a career development program for the study of psychiatric issues and interventions for people near the end-of-life, specifically major depressive disorders. The public health burden of issues such as depression at the end-of-life is enormous, not only for the patients, but their loved ones. Improved psychiatric care and interventions in this population would improve the lives of over a million people a year, allowing patients and families to be engaged in their final hours together, rather than to spend them in misery. Current evidence- based interventions for depression do not work fast enough or frequently enough for patients with only weeks to live. Small studies and our pilot work have provided initial evidence for the safety and efficacy of methylphenidate for rapidly treating depression in hospice settings. A mentoring team continuing to be led by Dilip Jeste and Charles von Gunten will guide the development of the candidate in the transformation from a successful basic scientist to an independent patient oriented researcher and clinical trialist, with a special focus on conducting clinical trials in vulnerable and medically-ill populations. The overall goal is to develop the candidate into an independent scientist who would obtain RO1 funding in a new and critically important area, psychiatric hospice and palliative care. This proposal is consistent with the NIMH strategic plan of strengthening the application of mental health interventions in diverse care settings by examining community and intervention delivery approaches , how they may affect intervention outcomes, and potentially providing a knowledge base to move evidence- based interventions into practice. SPECIFIC AIMS: In patients receiving hospice care with a current major depressive episode, a 28-day double-blind, comparator controlled, flexible dose trial of methylphenidate vs. citalopram monotherapy was conducted to assess both: 1) the comparative efficacy and onset of action, and 2) the comparative safety and tolerability of using these medications for treating major depressive episodes in this population. We hypothesized that treatment with methylphenidate would both: 1) Reduce the severity of depressive symptoms and 2) Induce a response of major depressive episodes significantly faster than citalopram. Methods: A 28-day double-blind, comparator controlled, flexible dose trial of methylphenidate monotherapy vs. citalopram monotherapy investigating the safety, tolerability, efficacy, and time to efficacy for the treatment of major depression in patients receiving hospice care was conducted. Doses were titrated to tolerable effects or side-effects in the first fifteen days. Patients remained on the final stable dose for the remainder of the study. As noted in the progress reports, this trial was a useful tool for training about clinical trial issues; however, the trial itself was cancelled due to lack of enrollment. Several other studies have been completed investigating ketamine for the rapid treatment of depression in hospice patients, as well as studies of cognitive impairments, hospice caregiver stress, and suicide in hospice patients. Conclusions: There are very few psychiatrists working in end-of-life care, and even fewer who are investigators. Continued funding of this proposal will give me the rest of the experience necessary to improve the science of recognizing and treating psychiatric issues at the end-of-life and become and independent investigator. Effective treatments have significant relevance for patients, their loved ones, and caregivers. Under this award, several studies have been completed looking at various psychiatric issues affecting those in hospice care, including two investigating the use of ketamine for the rapid treatment of depression in hospice patients. The results of these investigations will now be used for the remainder of this award to design and pilot larger-scale randomized controlled studies of patients with serious advanced illnesses receiving pre-hospice (palliative) care.